The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

John, Stephen G.; Owen, Paul; Harrison, L.; Szeto, Cheuk‐Chun; Lai, Ka-Bik; Li, Philip K.T.; McIntyre, Christopher W.

doi:10.2215/cjn.11211210

Cited by 15 publications

(19 citation statements)

References 27 publications

(30 reference statements)

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“…Significant endotoxaemia has been identified and described in the severe CKD and dialysis population [14,18]. ET levels seen in dialysis patients are extremely high, comparable with those reported in severe liver disease [19] and decompensated CHF [10].…”

Section: Discussionmentioning

confidence: 77%

Circulating Endotoxaemia and Frequent Haemodialysis Schedules

et al. 2014

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Background/Aims: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. Methods: A cross-sectional study of86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). Results: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. Conclusion: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.

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Section: Discussionmentioning

confidence: 77%

Circulating Endotoxaemia and Frequent Haemodialysis Schedules

et al. 2014

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“…For example, circulating endotoxin level significantly decreased with the introduction and optimization of antihypertensive therapy in both patients with and without CKD. 76 The reduction in endotoxin level was greater in patients without CKD despite similar drug usage and BP. 76 However, the reduction in endotoxin level did not correlate with the change in arterial PWVor hemodynamic status.…”

Section: Interventional Studiesmentioning

confidence: 90%

“…76 The reduction in endotoxin level was greater in patients without CKD despite similar drug usage and BP. 76 However, the reduction in endotoxin level did not correlate with the change in arterial PWVor hemodynamic status. 76 In patients on hemodialysis, plasma endotoxin level fell by one third within 4 weeks of conversion to ultrapure dialysate.…”

Section: Interventional Studiesmentioning

confidence: 90%

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

Szeto

McIntyre

2018

JASN

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Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.

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“…164 In a small study, optimized BP control with antihypertensive agents decreases endotoxin levels. 165 The mechanism of this beneficial effect is unknown.…”

Section: Miscellaneousmentioning

confidence: 99%

The Gut Microbiome, Kidney Disease, and Targeted Interventions

Ramezani

Raj

2014

Journal of the American Society of Nephrology

599

498

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The human gut harbors .100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.

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The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

Cited by 15 publications

References 27 publications

Circulating Endotoxaemia and Frequent Haemodialysis Schedules

Circulating Endotoxaemia and Frequent Haemodialysis Schedules

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

The Gut Microbiome, Kidney Disease, and Targeted Interventions

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